Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body

by Neil Shubin

  The bacterial past can be used to our advantage in studying the diseases of mitochondria—in fact, some of the best experimental models for these diseases are bacteria. This is powerful because we can do all kinds of experiments with bacteria that are not possible with human cells. One of the most provocative studies was done by a team of scientists from Italy and Germany. The disease that they studied invariably kills the infants who are born with it. Called cardioencephalomyopathy, it results from a genetic change that interrupts the normal metabolic function of mitochondria. In studying a patient who had the disease, the European team identified a place in the DNA that had a suspicious change. Knowing something about the history of life, they then turned to the microbe known as Paracoccus denitrificans, which is often called a free-living mitochondrion because its genes and chemical pathways are so similar to those of mitochondria. Just how similar was revealed by the European team. They produced the same change in the bacteria’s genes that they saw in their human patient. What they found makes total sense, once we know our history. They were able to simulate parts of a human mitochondrial disease in a bacterium, with virtually the same change in metabolism. This is putting a many-billion-year part of our history to work for us.

  The example from microbes is not unique. Judging by the Nobel Prizes awarded in medicine and physiology in the past thirteen years, I should have called this book Your Inner Fly, Your Inner Worm, or Your Inner Yeast. Pioneering research on flies won the 1995 Nobel Prize in medicine for uncovering a set of genes that builds bodies in humans and other animals. Nobels in medicine in 2002 and 2006 went to people who made significant advances in human genetics and health by studying an insignificant-looking little worm (C. elegans). Similarly, in 2001, elegant analyses of yeast (including baker’s yeast) and sea urchins won the Nobel in medicine for increasing our understanding of some of the basic biology of all cells. These are not esoteric discoveries made on obscure and unimportant creatures. These discoveries on yeast, flies, worms, and, yes, fish tell us about how our own bodies work, the causes of many of the diseases we suffer, and ways we can develop tools to make our lives longer and healthier.

  EPILOGUE

  As a parent of two young children, I find myself spending a lot of time lately in zoos, museums, and aquaria. Being a visitor is a strange experience, because I’ve been involved with these places for decades, working in museum collections and even helping to prepare exhibits on occasion. During family trips, I’ve come to realize how much my vocation can make me numb to the beauty and sublime complexity of our world and our bodies. I teach and write about millions of years of history and about bizarre ancient worlds, and usually my interest is detached and analytic. Now I’m experiencing science with my children—in the kinds of places where I discovered my love for it in the first place.

  One special moment happened recently with my son at the Museum of Science and Industry in Chicago. We’ve gone there regularly over the past three years because of his love of trains and the fact that there is a huge model railroad smack in the center of the place. I’ve spent countless hours at that one exhibit tracing model locomotives on their little trek from Chicago to Seattle. After a number of weekly visits to this shrine for the train-obsessed, Nathaniel and I walked to corners of the museum we had failed to visit during our train-watching ventures or occasional forays to the full-size tractors and planes. In the back of the museum, in the Henry Crown Space Center, model planets hang from the ceiling and space suits lie in cases together with other memorabilia of the space program of the 1960s and 1970s. I was under the presumption that in the back of the museum I would see the trivia that didn’t make it to the major exhibits up front. One display consisted of a battered space capsule that you could walk around and look inside. It didn’t look significant; it seemed way too small and jerry-rigged to be anything really important. The placard was strangely formal, and I had to read it several times before it dawned on me: here was the original Command Module from Apollo 8, the actual vessel that carried James Lovell, Frank Borman, and William Anders on humanity’s first trip to the moon and back. This was the spacecraft whose path I followed during Christmas break in third grade, and here I was thirty-eight years later with my own son, looking at the real thing. Of course it was battered. I could see the scars of its journey and subsequent return to earth. Nathaniel was completely disinterested, so I grabbed him and tried to explain what it was. But I couldn’t speak; my voice became so choked with emotion that I could barely utter a single word. After a few minutes, I regained my composure and told him the story of man’s trip to the moon.

  But the story I can’t tell him until he is older is why I became speechless and emotional. The real story is that Apollo 8 is a symbol for the power of science to explain and make our universe knowable. People can quibble over the extent to which the space program was about science or politics, but the central fact remains as clear today as it was in 1968: Apollo 8 was a product of the essential optimism that fuels the best science. It exemplifies how the unknown should not be a source of suspicion, fear, or retreat to superstition, but motivation to continue asking questions and seeking answers.

  Just as the space program changed the way we look at the moon, paleontology and genetics are changing the way we view ourselves. As we learn more, what once seemed distant and unattainable comes within our comprehension and our grasp. We live in an age of discovery, when science is revealing the inner workings of creatures as different as jellyfish, worms, and mice. We are now seeing the glimmer of a solution to one of the greatest mysteries of science—the genetic differences that make humans distinct from other living creatures. Couple these powerful new insights with the fact that some of the most important discoveries in paleontology—new fossils and new tools to analyze them—have come to light in the past twenty years, and we are seeing the truths of our history with ever-increasing precision. Looking back through billions of years of change, everything innovative or apparently unique in the history of life is really just old stuff that has been recycled, recombined, repurposed, or otherwise modified for new uses. This is the story of every part of us, from our sense organs to our heads, indeed our entire body plan.

  What do billions of years of history mean for our lives today? Answers to fundamental questions we face—about the inner workings of our organs and our place in nature—will come from understanding how our bodies and minds have emerged from parts common to other living creatures. I can imagine few things more beautiful or intellectually profound than finding the basis for our humanity, and remedies for many of the ills we suffer, nestled inside some of the most humble creatures that have ever lived on our planet.

  NOTES, REFERENCES, AND FURTHER READING

  CHAPTER ONE FINDING AN INNER FISH

  I have included a mix of primary and secondary sources for those interested in pursuing the topics in the book further. For accounts that use exploratory paleontological expeditions as a vehicle to discuss major questions in biology and geology, see Mike Novacek’s Dinosaurs of the Flaming Cliffs (New York: Anchor, 1997), Andrew Knoll’s Life on a Young Planet (Princeton: Princeton University Press, 2002), and John Long’s Swimming in Stone (Melbourne: Freemantle Press, 2006). All balance scientific analysis with descriptions of discovery in the field.

  The comparative methods that I discuss, including the methods used in our walk through the zoo, are the methods of cladistics. A superb overview is Henry Gee’s In Search of Deep Time (New York: Free Press, 1999). Basically, I present a version of the three-taxon statement, the starting point for cladistic comparisons. A good treatment with background sources is found in Richard Forey et al., “The Lungfish, the Coelacanth and the Cow Revisited,” in H.-P. Schultze and L. Trueb, eds., Origin of the Higher Groups of Tetrapods (Ithaca, N.Y.: Cornell University Press, 1991).

  The correlation between the fossil record and our “walk through the zoo” is discussed in several papers. A sampling: Benton, M. J., and Hitchin, R. (1997) Congruence between phylogenetic
and stratigraphic data in the history of life, Proceedings of the Royal Society of London, B 264:885–890; Norell, M. A., and Novacek, M. J. (1992) Congruence between superpositional and phylogenetic patterns: Comparing cladistic patterns with fossil records, Cladistics 8:319–337; Wagner, P. J., and Sidor, C. (2000) Age rank/clade rank metrics—sampling, taxonomy, and the meaning of “stratigraphic consistency,” Systematic Biology 49:463–479.

  The layers of the rock column and the fossils contained therein are beautifully and comprehensively discussed in Richard Fortey’s Life: A Natural History of the First Four Billion Years of Life on Earth (New York: Knopf, 1998). Resources for vertebrate paleontology include R. Carroll, Vertebrate Paleontology and Evolution (San Francisco: W. H. Freeman, 1987), and M. J. Benton, Vertebrate Paleontology (London: Blackwell, 2004).

  For the origin of tetrapods: Carl Zimmer reviewed the state of the art in the field in his highly readable and well-researched At the Water’s Edge (New York: Free Press, 1998). Jenny Clack has written the definitive text on the whole transition, Gaining Ground (Bloomington: Indiana University Press, 2002). The bible of this transition, Clack’s book will bring a novice to expert status quickly.

  Our original papers describing Tiktaalik appeared in the April 6, 2006, issue of Nature. The references are: Daeschler et al. (2006) A Devonian tetrapod-like fish and the origin of the tetrapod body plan, Nature 757:757–763; Shubin et al. (2006) The pectoral fin of Tiktaalik roseae and the origin of the tetrapod limb, Nature 757:764–771. Jenny Clack and Per Ahlberg had a very readable and comprehensive commentary piece in the same issue (Nature 757:747–749).

  Everything about our past is relative, even the structure of this book. I could have called this book “Our Inner Human” and written it from a fish’s point of view. The structure of that book would have been strangely similar: a focus on the history humans and fish share in bodies, brains, and cells. As we’ve seen, all life shares a deep part of its history with other species, while another part of its history is unique.

  CHAPTER TWO GETTING A GRIP

  Owen was by no means the first person to see the pattern of one bone–two bones–lotsa blobs–digits. Vicq-d’Azyr in the 1600s and Geoffroy St. Hilaire (1812) also made this pattern part of their worldviews. What distinguished Owen was his concept of the archetype. This was a transcendental organization of the body, reflecting the design of the Creator. St. Hilaire was searching less for an archetypical pattern hidden in all structure than for “laws of form” that govern the formation of bodies. A nice treatment of these issues is in T. Appel, The Cuvier-Geoffroy Debate: French Biology in the Decades Before Darwin (New York: Oxford University Press, 1987), and E. S. Russell, Form and Function: A Contribution to the History of Morphology (Chicago: University of Chicago Press, 1982).

  A recent volume edited by Brian Hall is one-stop shopping for information on limb diversity and development and contains a number of important papers on different kinds of limbs: Brian K. Hall, ed., Fins into Limbs: Evolution, Development, and Transformation (Chicago: University of Chicago Press, 2007). Useful references for exploring the shift from fins and limbs in more detail include Shubin et al. (2006) The pectoral fin of Tiktaalik roseae and the origin of the tetrapod limb, Nature 757:764–771; Coates, M. I., Jeffery, J. E., and Ruta, M. (2002) Fins to limbs: what the fossils say, Evolution and Development 4:390–412.

  CHAPTER THREE HANDY GENES

  The developmental biology of limb diversity has seen a number of reviews and primary papers. For a review of the classic literature see Shubin, N., and Alberch, P. (1986) A morphogenetic approach to the origin and basic organization of the tetrapod limb, Evolutionary Biology 20:319–387; and Hinchliffe, J. R., and Griffiths, P., “The Pre-chondrogenic Patterns in Tetrapod Limb Develoment and Their Phylogenetic Significance,” in B. Goodwin, N. Holder, and C. Wylie, eds., Development and Evolution (Cambridge, Eng.: Cambridge University Press, 1983), pp. 99–121. Saunders’s and Zwilling’s experiments are now classic, so some of the best accounts are now seen in the major textbooks in developmental biology. These include S. Gilbert, Developmental Biology, 8th ed. (Sunderland, Mass.: Sinauer Associates, 2006); L. Wolpert, J. Smith, T. Jessell, F. Lawrence, E. Robertson, and E. Meyerowitz, Principles of Development (Oxford, Eng.: Oxford University Press, 2006).

  For the first paper describing Sonic hedgehog’s role in limb patterning, go to Riddle, R., Johnson, R. L., Laufer, E., Tabin, C. (1993) Sonic hedgehog mediates the polarizing activity of the ZPA, Cell 75:1401–1416.

  Randy’s work on Sonic signaling in shark and skate fins is in Dahn, R., Davis, M., Pappano, W., Shubin, N. (2007) Sonic hedgehog function in chondrichthyan fins and the evolution of appendage patterning, Nature 445:311–314. Subsequent work from the lab on the origin of limbs, at least from a genetic perspective, is contained in Davis, M., Dahn, R., and Shubin, N. (2007) A limb autopodial-like pattern of Hox expression in a basal actinopterygian fish, Nature 447:473–476.

  The stunning genetic similarities in the development of flies, chickens, and humans is discussed in Shubin, N., Tabin, C., Carroll, S. (1997) Fossils, genes, and the evolution of animal limbs, Nature 388:639–648; and Erwin, D. and Davidson, E. H. (2003) The last common bilaterian ancestor, Development 129:3021–3032.

  CHAPTER FOUR TEETH EVERYWHERE

  The importance of teeth to an understanding of mammals is evident in the many treatments in the field. Dental structure plays a particularly important role in understanding the early record of mammals. Extensive reviews are found in Z. Kielan-Jaworowska, R. L. Cifelli, and Z. Luo, Mammals from the Age of Dinosaurs (New York: Columbia University Press, 2004); and J. A. Lillegraven, Z. Kielan-Jaworowska, and W. Clemens, eds., Mesozoic Mammals: The First Two-Thirds of Mammalian History (Berkeley: University of California Press, 1979), p. 311.

  Farish’s mammal from Arizona is analyzed in Jenkins, F. A., Jr., Crompton, A. W., Downs, W. R. (1983) Mesozoic mammals from Arizona: New evidence on mammalian evolution, Science 222:1233–1235.

  The tritheledonts we found in Nova Scotia are described in Shubin, N., Crompton, A. W., Sues, H.-D., and Olsen, P. (1991) New fossil evidence on the sister-group of mammals and early Mesozoic faunal distributions, Science 251:1063–1065.

  A recent review on the origin of teeth, bone, and skulls, in particular the new evolution gleaned from conodont animals, is found in Donoghue, P., and Sansom I. (2002) Origin and early evolution of vertebrate skeletonization, Microscopy Research and Technique 59:352–372. A thorough review of the evolutionary relationships among conodonts and their significance is in Donoghue, P., Forey, P., and Aldridge, R. (2000) Conodont affinity and chordate phylogeny, Biological Reviews 75:191–251.

  CHAPTER FIVE GETTING AHEAD

  A wonderfully comprehensive and detailed treatment of the details of skull structure, development, and evolution is found in a three-volume set: The Skull, James Hanken and Brian Hall, eds. (Chicago: University of Chicago Press, 1993). This is a multi-author update of one of the classic volumes on head development and structure: G. R. de Beer, The Development of the Vertebrate Skull (Oxford, Eng.: Oxford University Press, 1937).

  Details of head development and structure in humans can be found in texts on human anatomy and embryology. For embryology, see K. Moore and T.V.N. Persaud, The Developing Human, 7th ed. (Philadelphia: Elsevier, 2006). The companion anatomy text is K. Moore and A. F. Dalley, Clinically Oriented Anatomy (Philadelphia: Lippincott Williams & Wilkins, 2006).

  Francis Maitland Balfour’s seminal work is encapsulated in Balfour, F. M. (1874) A preliminary account of the development of the elasmobranch fishes, Q. J. Microsc. Sci. 14:323–364; F. M. Balfour, A Monograph on the Development of Elasmobranch Fishes, 4 vols. (London: Macmillan & Co., 1878); F. M. Balfour, A Treatise on Comparative Embryology, 2 vols. (London: Macmillan & Co., 1880–81); M. Foster and A. Sedgwick, The Works of Francis Maitland Balfour, with an introductory biographical notice by Michael Foster, 4 vols. (London: Macmillan & Co., 1885). A successor at Oxford, Edwin Goodri
ch, produced one of the classics of comparative anatomy, Studies on the Structure and Development of Vertebrates (London: Macmillan, 1930).

  Balfour, Oken, Goethe, Huxley, and others were addressing the problem known as head segmentation. Just as the vertebrae differ in a regular progression from front to back, so the head has a segmental pattern. A selection of classic and recent resources (all with good bibliographies) to pursue this field further: Olsson, L., Ericsson, R., Cerny, R. (2005) Vertebrate head development: Segmentation, novelties, and homology, Theory in Biosciences 124:145–163; Jollie, M. (1977) Segmentation of the vertebrate head, American Zoologist 17:323–333; Graham, A. (2001) The development and evolution of the pharyngeal arches, Journal of Anatomy 199:133–141.

  A recent overview of the genetic basis of gill arch formation is found in Kuratani, S. (2004) Evolution of the vertebrate jaw: comparative embryology and molecular developmental biology reveal the factors behind evolutionary novelty, Journal of Anatomy 205:335–347. Examples of the experimental manipulation of one gill arch into another, using genetic technologies, include Baltzinger, M., Ori, M., Pasqualetti, M., Nardi, I., Riji, F. (2005) Hoxa 2 knockdown in Xenopus results in hyoid to mandibular homeosis, Developmental Dynamics 234:858–867; Depew, M., Lufkin, T., Rubenstein, J. (2002) Specification of jaw subdivisions by Dlx genes, Science 298:381–385.

  A comprehensive, well-illustrated, and informative resource for early fossil records of skulls, heads, and primitive fish is reviewed in P. Janvier, Early Vertebrates (Oxford, Eng.: Oxford University Press, 1996). The paper describing Haikouella, the 530-million-year-old worm with gills, is Chen, J.-Y., Huang, D. Y., and Li, C. W. (1999) An early Cambrian craniate-like chordate, Nature 402:518–522.